Tics, Tourette s Disorder and ADHD Through the Lifespan

Transcription

1 Tics, Tourette s Disorder and ADHD Through the Lifespan February 27, 2013 ADHD Worldwide Conference Barbara J. Coffey, MD, MS Professor, Department of Psychiatry Icahn School of Medicine at Mount Sinai Chief, Tics and Tourette s Clinical and Research Program New York, New York Research Psychiatrist Nathan Kline Institute for Psychiatric Research Orangeburg, New York

2 Disclosures of Potential Conflicts ( ) Source Research Funding Boehringer Ingelheim X Catalyst X NIMH X Otsuka X TSA X Shire X Genco Sciences Advisor Consult X X Employee Speakers Bureau X Books, Intellectual Property In-kind Services (example: travel) Stock or Equity > $10,000

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4 Tics, Tourette s Disorder and ADHD Through the Lifespan Learning Objectives To review: Bidirectional overlap between ADHD and tic disorders Prevalence and impact of tic disorders and ADHD in youth and adults Update on relevant clinical science research on ADHD and tic disorders Treatment focus: use of stimulants in comorbid ADHD and tic disorders

5 Epidemiology: Bi-Directional Overlap of ADHD and Tic Disorders 1) Rates of tic disorders are higher (10-30%) in children with Attention Deficit Hyperactivity Disorder (ADHD) than in children without ADHD (1-10%) (Spencer, Biederman, Coffey et al., Arch Gen Psych; 1999, 56: ) 2) Rates of comorbid ADHD are high (50-75%) in clinically referred children with Tourette s Disorder (TD). (Coffey, Biederman, et al. J Nerv Ment Dis; 2000;188:583588; Freeman, TS International Data base Consortium; Eur Child Adolesc Psych 2007; 16 [suppl; 1];1/15-1/23) 3) Rates of ADHD in a TD community sample were higher (8.3%) than ADHD population prevalence (3.9%) (Apter et al, 1993; Scahill et al 2007)

6 Classification: DSM V: Neurodevelopmental Disorders: Motor Disorders vs. DSM-IV-TR 2000 Tic Disorders Transient tic disorder: one or more tics present for greater than 4 weeks, but less than 12 months Provisional tic disorder: Single or multiple motor tics and/or vocal tics; present for less than 1 year since first tic onset. Onset before age 18. Chronic motor or vocal tic disorder: one or more motor or vocal tics present for greater than 1 year Tourette s Disorder. Both multiple motor and one or more vocal tics have been present at some time during the illness, although not necessarily concurrently. Tics occur many times a day (usually in bouts), nearly every day or intermittently throughout a period of more than 1 year, and during this period there was never a tic-free period of more than 3 consecutive months. Onset before 18 years. The tics may wax and wane in frequency but have persisted for more than a year since first tic onset. Tic Disorder Not Otherwise Specified Unspecified Tic Disorder 6

7 Tics and Tourette s Disorder: Epidemiology (Scahill et al; Morbidity and Mortality Weekly Report CDC; 2009) CDC Prevalence of Diagnosed TS in Youth age 6-17 in 2007 in US (National Study of Children s Health) 0.3-1% in US 3x more common in boys than girls 2x more frequently diagnosed age vs. 6-11

8 Prevalence of diagnoses age 6-17 years: ever received a diagnosis of Tourette syndrome (TS), by parent report (National Survey of Children's Health, United States, 2007) Among children ever diagnosed with TS, 79% also had been diagnosed with at least one other selected diagnosis. Among children who currently have TS, 73% currently have at least one additional selected diagnosis. ADHD, by parent report. ** Such as oppositional defiant disorder or conduct disorder, by parent report.

9 CorticoStriatoPUTAMEN PallidoThalamic Circuit GLOBUS PALLIDUS THALAMUS 9

10 TD and ADHD: Neurobiology (Seidman et al; Biol Psychiatry; 2005; 57; ; Sukhodolsky et al; Eur Child Adolesc Psychiatry 2007;16:1/51-1/59; Leckman et al; JCAP, 2010; 20 (4); ; Dickstein et al; J Child Psych Psych; 2006: 47: ) *Inhibition is a core deficit in both disorders Executive functions abnormalities in both thought to result from fronto-striatal and frontal-parietal network dysfunction ADHD: In youth, smaller volumes reported in DLPC, caudate, pallidum, corpus callosum and cerebellum (Seidman et al; 2005) ADHD: Across studies, significant patterns of frontal hypoactivity reported, including ACC, DLPC, inferior prefrontal, and related regions: basal ganglia, thalamus and parietal cortex.

11 TD and ADHD: Neurobiology (Seidman et al; Biol Psychiatry; 2005; 57; ; Sukhodolsky et al; Eur Child Adolesc Psychiatry 2007;16:1/51-1/59; Leckman et al; JCAP, 2010; 20 (4); ; Dickstein et al; J Child Psych Psych; 2006: 47: ) TD: Approximate 5% reduction in caudate volume reported in both children and adults with TD (Peterson et al; 2003). Inverse correlation between caudate volume in childhood and tic severity in early adulthood (Bloch et al; 2005) Cortical thinning in youth reported in sensory and motor areas, correlating with worst ever tic severity (Sowell et al; 2008). TD+ ADHD: CTSC misguided neural oscillations may result in BG disinhibition, worsened by frontal hypoactivity in ADHD. Since both TD and ADHD improve with time, may be due to increased myelinization of prefrontal regions.

12 Wang et al. 2011

13 Characteristics of the final TS Genome-wide Association Study samples: (Scharf et al; Molecular Psychiatry; 2012; 1-8) Findings: no markers achieved a genome wide threshold of significance

14 Genome-wide association study of Tourette syndrome (Scharf et al 2012)

15 Tourette s Disorder: Natural History and Course: Does it Remit or Persist? What About Comorbidity? DSM IV-TR American Psychiatric Association (2000) Course:.The duration of the disorder is usually lifelong, though periods of remission lasting from weeks to years may occur.. Tic severity: Research in the past decade suggests peak severity occurs at about age years with improvement into adolescence (retrospective birth cohort design) (Leckman et al. Pediatrics. 1998; Coffey et al. JNMD. 2004)

16 Time Course of Tic Severity Ratings (Leckman, Zhang, et al. Pediatrics. 1998;102:14-19)

17 Course of ADHD and Tic Disorders: What Happens to Tics in the Context of ADHD Over Time? (Spencer, Biederman, Coffey, et al. Arch Gen Psych 1999, 56: ) Design: Prospective ADHD follow-up Objective: To evaluate the prevalence and impact of tic disorders at baseline and at follow-up on the course of ADHD. Methods: N=128 boys with ADHD; N=110 controls. Duration of follow-up: 4 years. Results: Proportion of ADHD youth with tics: 34% Remission rate for tics over 4 years: 65% Remission rate for ADHD: 20% Conclusion: Tic remission rate is independent of ADHD Tic disorders did not impact ADHD course

18 % Rates of Tic Disorders in ADHD & Control Probands ** ** ADHD Controls ADHD Controls Baseline Follow-up *** ADHD Control s Overall

19 Onset of ADHD and Tic Disorders in ADHD Probands % ADHD Tic Disorders Age in Years

20 % Offset of ADHD and Tic Disorders in ADHD Probands ADHD Tic Disorders Age in Years

21 Informativeness of Structured Diagnostic Interviews in the Identification of Tourette s Disorder in Referred Youth (Coffey, B. et al.j. Nerv. Ment. Dis. 2000; Sep;188 (9): ) Clinical and Demographic Characteristics of Non-specialized and Specialized Clinic Patients with TD Current Age SES Past GAS Current GAS % Male Non-specialized Clinic patients (N=92) Mean SD N % Specialized Clinic patients (N=103) Mean SD N % Overall Significance p p

22 Comorbidity: Disruptive Behavior Disorders Non-specialized Clinic Patients Specialized Clinic Patients (N = 92) (N = 103) Overall Significance Diagnosis N % N % p ADHD Conduct Disorder Oppositional Defiant Disorder Any Disruptive Disorder *Pure TD (Non-comorbid)

23 Anxiety Disorders Non-specialized Clinic Patients Specialized Clinic Patients (N = 92) (N = 103) Overall Significance Diagnosis N % N % p Panic Disorder Agoraphobia Social Phobia Simple Phobia OCD Separation Anxiety Multiple Anxiety Disorders (2+)

24 Developmental Course of Tourette s Disorder and ADHD Developmental Psychopathology of Children and Adolescents with Tourette Syndrome-Impact of ADHD (Roessner et al. Eur Child Adolesc Psych; 2007; 16;1/24-1/25) Design and Subjects: TS International Data Base Consortium N=5060 patients in 67 tertiary centers in 27 countries:. Cross-sectional design; youth age 5-17 years Findings: 1. Higher rate of comorbidity in TD+ADHD than TDADHD in children and adolescents 2. Rate of OCD was higher in TD+ADHD in children (age 5-10) but not adolescents (age 11-17). 3. But OCD developed more rapidly year to year in the TD-ADHD group

25 Year-wise changes of the rate of comorbidities in children and adolescents with TD versus TD+ADHD in (a) number of comorbidities and (b) obsessive compulsive disorder Roessner, Eur Child Adolesc Psychiatry, 2007

26 Developmental Course of Tourette s Disorder and ADHD (Roessner et al. Eur Child Adolesc Psych; 2007; 16;1/24-1/25) International Data Base Consortium. N=5060 patients in 67 tertiary centers in 27 countries: TS. Cross-sectional; youth age 5-17 years 1. Rate of comorbid ODD/CD was higher in youth with TD+ ADHD than TD-ADHD 1. Mood disorders were more frequent in children with TD+ ADHD, but the rate of increase was independent of ADHD 2. Anxiety disorders were slightly more frequent in TD+ ADHD in children, but not in adolescents; rate of anxiety disorders rose more rapidly in TD-ADHD

27 Year-wise changes of the rate of comorbidities in children and adolescents with TD versus TD+ADHD in (c) anxiety disorders, (d) conduct disorders/oppositional defiant disorder, (e) mood disorders Roessner, Eur Child Adolesc Psychiatry, 2007

28 Tourette Syndrome in Youth with and without OCD and ADHD (Lebowitz, E. Motlagh, M. Katsovich, L. King, R. Lombroso, Grantz, H. Line, H. Bentley, M. Gibert, D. Singer, H. Coffey, B. TSSG, Kurlan, R. Leckman, J. Eur Child Adolesc Psych 2012; 21: ) Design: Compared TS only with TS+ADHD and TS+OCD. N=158 youth. 53% TS+OCD, 39% TS+ADHD, 24% both Results: TS+OCD had more severe tics, more depression and anxiety, poorer global functioning TS+ADHD: same tic severity, but greater psychosocial stress, more externalizing behaviors, and poorer global functioning Conclusion: More research is needed on TS subtypes.

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30 Lebowitz et al. 2012

31 Disentangling Effects of Tourette Syndrome and ADHD on Cognitive and Behavioral Phenotypes (Rizzo, R. Curatolo, P. Gulisano, M. Virzi, M. Arpino, C. Robertson, M. Brain and Development; 2007; 29; ) Design: N=80 youth, age 6-16 years, in 4 groups: TS only, ADHD only, TS+ADHD, controls. Results: All cases differed significantly from controls. TS only did not differ from controls in behavioral ratings or IQ. ADHD, with or without TS, was associated with more behavioral problems and lower IQ. No difference in affective and anxiety symptoms between three case groups, but differed from controls. TS patients were found to be more delinquent than controls. Conclusions: May be additive effect of ADHD and TS.

32 Rizzo et al. 2007

33 Tourette Syndrome-Associated Psychopathology: Roles of Comorbid ADHD and OCD (Pollak, Y. Benarroch, F. Kanengisser, L. Shilon, Y. Benpazi, H. Shalev, R. Gross-Tsur, V. Dev Behav Pediatr; 2009; 30; ) Aim: Evaluate impact of tic, ADHD and OCD on CBCL externalizing and internalizing disorders Design: Chart review of 180 TS subjects, age 15-18, in Neuropediatric Clinic. Compared CBCL in TS only, ADHD only, TS+ADHD and controls. Results: Highest prevalence of externalizing in TS+ADHD>ADHD>TS only>controls Highest prevalence of internalizing in TS+ADHD>TS only>adhd>controls. Conclusion: Tics, ADHD and OCD differentially effect variance in internalizing and externalizing problems, and TS only is a risk factor for behavioral problems.

34 Psychosocial Outcome and Psychiatric Comorbidity in Older Adolescents with Tourette Syndrome (Gorman, D. Thompson, N. Plessen, K. Robertson, M. Leckman, J. and Peterson, B.; Br J Psych; 2010; 197; 36-44) Aim: To compare psychosocial outcome and lifetime comorbidity rates in older adolescents with TD and controls Design: N=65 with TD identified in childhood, and 65 matched community controls, assessed at age 18 Results: Compared with controls, TD individuals had substantially lower CGAS scores and higher rates of ADHD, MDD, and CD (p <0.01). In those with TD, poorer psychosocial outcomes were associated with greater ADHD, OCD and tic severity. Conclusion: Clinically referred youth with TD have impaired psychosocial outcome and high comorbidity rates in late adolescence.

35 Comparison of lifetime psychiatric disorders in the Tourette syndrome group and community controls Gorman, BJ Psych, 2010

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37 Impact of Tic Disorders on ADHD Outcome Across the Life Cycle: Findings from a Large Group of Adults With and Without ADHD (Spencer, Biederman, Faraone, Mick, Coffey, et al. Am J Psych 2001; 158: ) Objective: To assess impact of presence of tic disorder on the course of ADHD in adults. Methods: Blinded, retrospective assessment by Structured Clinical Interview for DSM IV (SCID), supplemented with modules from the K-SADS-E covering childhood diagnoses. N=312 adults with ADHD; N=252 adult controls Results: Significantly greater proportion of adults with ADHD (12%) than those without ADHD (4%) had tic disorders Tic disorders followed mostly a remitting course and had little impact on functional capacities. Conclusion: Adult findings confirm and extend previous findings in youth with ADHD, documenting that although individuals with ADHD are at greater risk for tic disorders, the presence of tics has limited impact on ADHD outcome.

38 Adults with Tourette Syndrome with and without Attention Deficit Hyperactivity Disorder (Haddad, A. Umoh, B. Robertson, M. Acta Psychiatr Scand; 2009; 120; ) Design: N=80 adults with TS only were compared to 64 with TS+ADHD in a clinical interview and standardized measures of depression, anxiety and OCD Results: No differences in tic severity. TS+ADHD had significantly more depression, anxiety, OCD and behavioral problems than TS only. Conclusion: More overall behavioral problems and psychopathology in adults with TS+ADHD vs TS only is consistent with findings in children. ADHD treatment in childhood may prevent development of behavioral problems later in life.

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40 Haddad et al. 2009

41 Diagnostic Evaluation: Tics and ADHD Structured diagnostic interviews, interviews such as the Children's Schedule for Affective Disorders and Schizophrenia (K-SADS) can improve classification and assessment of comorbidity. Standardized rating scales have improved diagnostic reliability in research studies; helpful in clinical care. The Yale-Global Tic Severity Scale (YGTSS) (Leckman, Riddle, Hardin, Ort, Swartz, Stevenson, et al., 1989) is considered gold standard. The YGTSS assesses domains of tic number, frequency, intensity,

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44 TD/Tics + ADHD: Treatment Issues Tics: Most patients with mild tic symptoms need only monitoring, education, and guidance. Tic symptoms need to be treated if causing distress and/or impairment. In US there are only two formally approved medications: haloperidol and pimozide. ADHD: Since ADHD symptoms are more likely to persist and cause significant functional impairment, treatment is usually necessary. What s new? Behavioral treatment of tics (habit reversal training) is now established. But there are no published studies of combination pharmacotherapy and behavioral treatment in comorbid ADHD and

45 ADHD and Tics/TD: Can We Treat with Stimulants? Old studies suggested that stimulants increase tics, (Lowe et al. 1980) and US pharmaceutical labeling states tics are a contraindication for stimulants (PDR, 2012) Recent studies demonstrated that some TD patients with significant ADHD may be candidates for methylphenidate (MPH) when no other treatments have been effective (Gadow, Nolan, Sverd. 1992; Gadow et al. 2007; TSSG; 2002)

46 % Onset of Tic Disorders in ADHD Probands Stratified by Stimulant Treatment (Spencer, Biederman, Coffey, et al. Arch Gen Psych 1999, 56: ) Stimulant Treated Not Stimulant Treated Age in Years 20 25

47 % Offset of Tic Disorders in ADHD Probands Stratified by Stimulant Treatment (Spencer, Biederman, Coffey, et al. Arch Gen Psych 1999, 56: ) Not Stimulant Treated Stimulant Treated Age in Years 20 25

48 Treatment of ADHD and Tics (TACT): Targeted Combined Pharmacotherapy Study (TSSG. TACT. Neurology. 2002; 58: ) NINDS-sponsored multicenter study of clonidine and methylphenidate (MPH) in the treatment of children with ADHD and Tourette s disorder or chronic tics (TACT) Design: 136 children (ages 7-14) were treated in the 16-week, double-blind, placebo-controlled protocol Hypotheses: Methylphenidate and clonidine both individually and in combination are more effective than placebo for treatment of ADHD and tics in Tourette s Disorder Procedures: Clonidine MPH Treatment Phase or Pbo or Pbo BL 4 wk 8 wk 12 wk 16 wk

49 TACT Study: Results (TSSG, TACT. Neurology. 2002;58: ) ADHD (Teacher Conners): Compared to placebo, greatest benefit for CLON + MPH (p < ); significant improvement in CLON (p < 0.002) and MPH (p < 0.003) groups CLON: best for hyperactivity and impulsivity; MPH for inattention Tics (YGTSS): severity reduced in all treatment groups vs. placebo; order was CLON + MPH > CLON > MPH Mean doses of each drug were low: 0.25 CLON / 26 MPH Adverse Effects: No difference in % of MPH (20%), CLON (26%) and PBO (22%) groups with worsening of tics There were no safety issues, particularly cardiovascular

50 Meta-Analysis: Treatment of Attention Deficit Hyperactivity Disorder in Children with Comorbid Tic Disorders (Bloch, M. Panza, K. Landeros-Weisenberger, A. and Leckman, J. JAACAP. 2009; 48 (9); ) Aim: To determine relative efficacy of medications to treat ADHD and tic symptoms in children with both TD and ADHD. Design: PubMed search for all double blind, RCTs in children with ADHD and tics using random effects meta-analysis with standardized mean difference as primary outcome for effect size. Results: N=9 studies with 477 subjects. N=6 medications: dextroamphetamine, methylphenidate, alpha 2 agonists (clonidine and guanfacine), desipramine, atomoxetine, and deprenyl.

51 Meta-Analysis: Treatment of Attention Deficit Hyperactivity Disorder in Children with Comorbid Tic Disorders (Bloch, M. Panza,K. Landeros-Weisenberger, A. and Leckman, J. JAACAP. 2009; 48 (9); ) Results: Methylphenidate, alpha 2 agonists, desipramine, and atomoxetine showed efficacy in improving ADHD symptoms in children with comorbid tics. Alpha agonists and atomoxetine significantly improved comorbid tics Supra-therapeutic doses of dextroamphetamine increase tics. There is no evidence that methylphenidate worsened tic severity in the short term.

52 Methylphenidate effect on ADHD (A) and tic severity (B) Bloch, JAACAP, 2009

53 Alpha-2 agonist effect on ADHD (A) and tic severity (B) Bloch, JAACAP, 2009

54 Meta-Analysis: Effectiveness of medication in treating ADHD and tic disorders Bloch, JAACAP, 2009

55 Meta-Analysis: Treatment of Attention Deficit Hyperactivity Disorder in Children with Comorbid Tic Disorders (Bloch, M. Panza,K. Landeros-Weisenberger, A. and Leckman, J. JAACAP. 2009; 48 (9); ) Conclusion: Methylphenidate seems to offer the best and most immediate improvement of ADHD and does not seem to worsen tics. Alpha agonists offer the best combination of improvement in both tics and ADHD symptoms. Atomoxetine and desipramine provide additional evidence based treatment of ADHD in children with comorbid tics. Supra-therapeutic doses of dextroamphetamine should be avoided.

56 Comprehensive Behavioral Intervention for Tics Study (CBITS) or Habit Reversal Therapy (Piacentini, J. Woods, D. Scahill et al. JAMA; 2010;303 (19): ) Two parallel studies compared behavior therapy to supportive therapy (ST) Child study: 126 children (ages 9-17) with TD/CTD; JAMA; 2010 Adult study: 120 children and adults (ages 16+) with TD/CTD: Arch Gen Psych; 2012 Three phases: 1) Awareness training 2) Competing response training 3) Social support **In CBIT child study, children with ADHD did not do as well (lower ES) as those without ADHD. 56

57 Responder Status at Week 10: Effect Size 0.68 (CGI-Improvement = 1 or 2) Courtesy of Piacentini, J. AACAP 2009 CBIT PST p <

58 Testing Tic Suppression: Comparing the Effects of Dexmethylphenidate to No Medication in Children and Adolescents with ADHD and TD (Lyon,G. Samar,S. Conelea, C. et al JCAP; 2010; (4) ) Aim: To test whether single dose, immediate release (IR) dexmethylphenidate (d-mph) can facilitate behavioral tic suppression in youth with ADHD and TD Hypothesis: D-MPH would facilitate tic suppression compared to no medication Design: N=10 children in a random cross-over design were administered d-mph on one visit and no medication on another. Following baseline, subjects were reinforced for suppressing tics using a behavioral reinforcement tic suppression paradigm (Woods et al; 2005) Children were reinforced for suppressing tics with tokens from a Tic Detector for 5 minute intervals

59 Sociodemographic Data: Testing Tic Suppression Lyon, JCAP, 2010

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61 Testing Tic Suppression: Yale Global Tic Severity Scale Subscale Scores by Study Condition Lyon, JCAP, 2010

62 Testing Tic Suppression: Mean number of tics per minute under the non-medication and one-time dose of d-mph conditions during the TSP Lyon, JCAP, 2010

63 Testing Tic Suppression: Comparing the Effects of Dexmethylphenidate to No Medication in Children and Adolescents with ADHD and TD (Lyon,G. Samar,S. Conelea, C. et al JCAP; 2010; (4) ) Results: Relative to no medication, tics were reduced when subjects were given a single dose of d-mph. Behavioral reinforcement of tic suppression resulted in lower tic rates compared to baseline, but d-mph did not enhance this suppression. Conclusion: Results replicate prior studies of behavioral tic suppression in youth with TD without ADHD Tic reduction (vs. exacerbation) with acute d-mph challenge.

64 New Combination Pharmacotherapy and Behavioral Treatment Study: Improving Tic-Related Response Inhibition: Comparing the Effects of MPH alone vs. MPH + HRT in Children and Adolescents with ADHD and CTDs

65 HRT2 Subjects: Preliminary Data Subject Phase A (Stimulant optimization ) Guanfacine + Dex-MPH Phase B (HRT) No Yes Yes 2 Dex-MPH Yes 3 Lisdexamphetamin e No Yes Yes 4 Guanfacine + Oros MPH Yes Still in treatment Still in treatment 5 Clonidine Not yet 6 Guanfacine; could not tolerate stimulant or clonidine monotherapy Not yet Preliminary Parent management Preliminary Parent management Preliminary Parent management Preliminary Parent management 1 Endpoint Endpoint ADHD Tics (CGI 1 or 2) (CGI 1 or 2) Yes Yes

66 Tics, Tourette s Disorder, and ADHD Through the Lifespan: Summary **There is bi-directional overlap of ADHD and Tic Disorders, including common neural substrates and phenomenology. Prevalence of ADHD in TD in clinically referred samples is 50-75%, and tics in ADHD patients 10-30%. ADHD symptoms persist, but tic symptoms tend to remit over time. Much of the associated psychopathology (behavioral, neurocognitive) in Tourette s Disorder is secondary to ADHD Most clinically referred patients with ADHD and tic disorders will need treatment for ADHD, and tics may or may not need treatment. Alpha agonist is recommended as initial pharmacotherapy for ADHD + tics when tics are the primary issue Recent meta-analysis reveals that methylphenidate is effective in treatment of ADHD in children with ADHD and tics, and does not increase tics in the short run Future study directions: combination pharmacotherapy and behavioral treatment (HRT), long acting stimulants and alpha agonists in ADHD/ tic disorders, predictors of tic exacerbations on stimulants

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68 Icahn School of Medicine at Mount Sinai Tics and Tourette s Clinical and Research Program/Division of Tics, OCD and Related Disorders (DTOR) Wayne Goodman, M.D. Professor and Chair, Department of Psychiatry, Mount Sinai School of Medicine, Director, Division of Tics, OCD and Related Problems Vilma Gabbay, M.D. M.S Associate Professor, Department of Psychiatry, Director, Pediatric Mood and Anxiety and Disorders Clinical Research Program Dorothy Grice, M.D. Professor, Department of Psychiatry, Director, Pediatric OCD Program Matthew Hopperstad, M.D Assistant Professor, Department of Psychiatry Ariz Rojas, Ph.D. Assistant Professor, Department of Psychiatry Resham Gellatly, B.A. Research Coordinator, MSSM Laura Ibanez, B.A. Research Assistant (Nathan Kline Institute and MSSM) Lindsay Farmer. B.A., Research Intern, MSSM NYU School of Medicine Collaborators: Ruth Nass, M.D.. Xavier Castellanos, M.D. Jonathan Brodie, M.D. Ph.D. Gholson Lyon, M.D. Ph.D. Stephanie Samar, M.A. 68